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SMART-DAPPER: Leveraging the Depression And Primary-care Partnership for Effectiveness-implementation Research Project (SMART-DAPPER)

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ClinicalTrials.gov Identifier: NCT03466346
Recruitment Status : Not yet recruiting
First Posted : March 15, 2018
Last Update Posted : January 16, 2019
Sponsor:
Collaborators:
University of Nairobi
National Institute of Mental Health (NIMH)
Kenya Medical Research Institute
University of California, San Diego
Makerere University
Information provided by (Responsible Party):
Susan Meffert, University of California, San Francisco

Brief Summary:
Despite carrying the vast majority of the global mental disorder burden, 75% of adults with mental disorders in Low and Middle Income Countries have no access to services. This study will test strategies for integrating first and second line evidence-based depression and trauma-related disorder treatments with primary care services at a large public sector hospital and conduct robust cost and cost-benefit analyses of each treatment to produce a "menu" of cost-benefit options for personalized, integrated mental health care with corresponding effectiveness and implementation values.

Condition or disease Intervention/treatment Phase
Depression, Unipolar Posttraumatic Stress Disorder Trauma Drug: Fluoxetine Behavioral: Interpersonal Psychotherapy Not Applicable

Detailed Description:

Mental disorders are a leading cause of global disability, driven by depression and anxiety. Most of the disease burden is in Low and Middle Income Countries (LMICs), where 75% of adults with mental disorders have no service access. Despite nearly 15 years of efficacy research showing that local non-specialists can provide evidence-based care for depression and anxiety in LMICs, few studies have advanced to the critical next step: identifying strategies for sustainable "real world" non-specialist treatment including integration with existing healthcare platforms and response to common clinical dilemmas, such as what treatment to start with and how to modify it.

Given the need to personalize treatment to achieve remission (absence of disease) and the scarcity of mental health specialists in LMICs, successful reduction of population-level disability caused by depression and anxiety requires (1) evidence-based strategies for first-line and second-line (non-remitter) treatment delivered by non-specialists, with (2) confirmation of presumed mechanism of action and (3) patient-level moderators of treatment outcome to inform personalized, non-specialist treatment algorithms.

The research team has worked in western Kenya for 6 years with a UCSF-Kenya collaboration that supports integrated HIV services at over 70 primary healthcare facilities in Kisumu County (Family AIDS Care and Education Services [FACES]). Primary care populations in Kenya have high prevalence of Major Depressive Disorder (MDD) (26%) and Posttraumatic Stress Disorder (PTSD) (35%). Kenyan leaders lack an evidence base for two essential treatments - psychotherapy and second generation antidepressants- without which scale-up will fall short of its potential. We conducted a randomized, controlled trial in Kisumu County of Interpersonal Psychotherapy (IPT) delivered by non-specialists for HIV-positive patients with MDD and PTSD. In our study, IPT achieved full remission of MDD and PTSD in the majority of participants.

Given the high prevalence of MDD-PTSD co-morbidity, we will collaborate with the FACES team providing services to Kisumu County Hospital (KCH) primary care outpatient clinic (~10,000 patients/month) to conduct a randomized trial of IPT versus fluoxetine for MDD and/or PTSD. Local non-specialists will be trained in mental health care for the SMART and hired through the Kenyan Ministry of Health to work at KCH. SMART participants will be randomized to: (1) first line treatment with IPT or fluoxetine; (2) second line treatment for non-remitters— treatment "switch" (e.g., IPT to fluoxetine) or treatment "combination" (e.g., addition of IPT to fluoxetine). Research with mental health specialists in high income countries suggests that antidepressants and psychotherapy have equivalent short-term efficacy and that psychotherapy yields superior long-term relapse prevention. We will test the role of previously identified mechanisms in mediating remission and key moderators of treatment effect. Results of moderator and Q learning analyses will produce first and second-line non-specialist treatment algorithms.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 2710 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: fluoxetine versus interpersonal psychotherapy (IPT) for treatment of Major Depressive Disorder (MDD) and/or Posttraumatic Stress Disorder (PTSD)
Masking: Single (Outcomes Assessor)
Masking Description: participants will be evaluated by an outcomes assessor that is not aware of which treatment the participant is receiving. This will be achieved by keeping the randomization key locked and accessible only to the study coordinator and investigators. Participants who are scheduled for assessments will be reminded not to spontaneously disclose their treatment modality to the outcomes assessor.
Primary Purpose: Health Services Research
Official Title: A Sequential, Multiple Assignment Randomized Trial (SMART) for Non-specialist Treatment of Common Mental Disorders in Kenya: Leveraging the Depression And Primary-care Partnership for Effectiveness-implementation Research (DAPPER) Project
Estimated Study Start Date : March 2019
Estimated Primary Completion Date : January 2023
Estimated Study Completion Date : June 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Fluoxetine

Arm Intervention/treatment
Active Comparator: Interpersonal psychotherapy
IPT was developed in the 1980s by Gerald Klerman and Myrna Weissman to address interpersonal issues in depression. IPT is now considered evidence-based, first-line treatment for depression. IPT improves symptoms by addressing problems in social relationships. IPT is traditionally delivered as weekly one-hour sessions over 12 weeks, focused on one interpersonal problem area.
Behavioral: Interpersonal Psychotherapy
PT was developed in the 1980s by Gerald Klerman and Myrna Weissman to address interpersonal issues in depression. IPT is now considered evidence-based, first-line treatment for depression. IPT improves symptoms by addressing problems in social relationships. IPT is traditionally delivered as weekly one-hour sessions over 12 weeks, focused on one interpersonal problem area.
Other Name: IPT

Active Comparator: fluoxetine
Fluoxetine is a selective serotonin reuptake inhibitor that is FDA approved for the treatment of depression. Compared to placebo, fluoxetine is more likely to produce symptom response for MDD. Despite the interim development of many other antidepressants since the development of fluoxetine, it remains a first line treatment for depression.
Drug: Fluoxetine
Fluoxetine is a selective serotonin reuptake inhibitor that is FDA approved for the treatment of depression. Compared to placebo, fluoxetine is more likely to produce symptom response for MDD. Despite the interim development of many other antidepressants since the development of fluoxetine, it remains a first line treatment for depression.

Active Comparator: Fluoxetine after IPT
participants who do not remit from MDD and PTSD after treatment with IPT may be randomized to fluoxetine.
Drug: Fluoxetine
Fluoxetine is a selective serotonin reuptake inhibitor that is FDA approved for the treatment of depression. Compared to placebo, fluoxetine is more likely to produce symptom response for MDD. Despite the interim development of many other antidepressants since the development of fluoxetine, it remains a first line treatment for depression.

Active Comparator: IPT after fluoxetine
participants who do not remit from MDD and PTSD after treatment with fluoxetine may be randomized to IPT.
Behavioral: Interpersonal Psychotherapy
PT was developed in the 1980s by Gerald Klerman and Myrna Weissman to address interpersonal issues in depression. IPT is now considered evidence-based, first-line treatment for depression. IPT improves symptoms by addressing problems in social relationships. IPT is traditionally delivered as weekly one-hour sessions over 12 weeks, focused on one interpersonal problem area.
Other Name: IPT

Active Comparator: IPT + fluoxetine
participants who do not remit from MDD and PTSD after treatment with fluoxetine may be randomized to IPT + fluoxetine.
Drug: Fluoxetine
Fluoxetine is a selective serotonin reuptake inhibitor that is FDA approved for the treatment of depression. Compared to placebo, fluoxetine is more likely to produce symptom response for MDD. Despite the interim development of many other antidepressants since the development of fluoxetine, it remains a first line treatment for depression.

Behavioral: Interpersonal Psychotherapy
PT was developed in the 1980s by Gerald Klerman and Myrna Weissman to address interpersonal issues in depression. IPT is now considered evidence-based, first-line treatment for depression. IPT improves symptoms by addressing problems in social relationships. IPT is traditionally delivered as weekly one-hour sessions over 12 weeks, focused on one interpersonal problem area.
Other Name: IPT




Primary Outcome Measures :
  1. Change in the Mini International Psychiatric Interview (MINI) depression module [ Time Frame: baseline, 1.5, 3, 6, 9, 12, 18, 24 and 30 months ]
    Change in the diagnostic measure of major depressive disorder

  2. Change in the Mini International Psychiatric Interview (MINI) PTSD module [ Time Frame: baseline, 1.5, 3, 6, 9, 12, 18, 24 and 30 months ]
    Change in the diagnostic measure of PTSD


Secondary Outcome Measures :
  1. Cost Effectiveness [ Time Frame: baseline, 1.5, 3, 6, 9, 12, 18, 24 and 30 months ]
    cost of treatment including opportunity costs (e.g., transport, childcare, lost wages) provider time, other healthcare utilization/hospitalizations

  2. Cost Benefit [ Time Frame: baseline, 1.5, 3, 6, 9, 12, 18, 24 and 30 months ]
    ratio of economic gains and costs associated with each intervention arm



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Kisumu County Hospital (KCH) adult primary care outpatient clinic attendees who screen positive for MDD on the Mini International Neuropsychiatric Interview (MINI); and/or PTSD on the MINI
  2. Ability to attend weekly IPT sessions/fluoxetine monitoring; (3) 18 years or older

Exclusion Criteria:

  1. Cognitive dysfunction compromising ability to participate in IPT or accurately take fluoxetine (lack of orientation to person, place, time and situation)
  2. acute suicidality (moderate or high score on the MINIsuicidality module) requiring higher level of care
  3. drug/alcohol use disorders requiring substance use treatment (AUDIT score of 8 or higher, DAST score of 3 or higher)
  4. history of mania or requiring treatment for hypomania (positive score on MINI mania/hypomania module)
  5. Outside mental health treatment during the study treatment phases (any mental health treatment is allowed during follow-up phases and is recorded by study team).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03466346


Contacts
Contact: Susan M Meffert, MD, MPH 4154767532 Susan.meffert@ucsf.edu
Contact: Linnet Ongeri, MBChB, MMed +254 0722615999 linongeri@gmail.com

Sponsors and Collaborators
University of California, San Francisco
University of Nairobi
National Institute of Mental Health (NIMH)
Kenya Medical Research Institute
University of California, San Diego
Makerere University
Investigators
Principal Investigator: Muthoni J Mathai, MDChB, MMed University of Nairobi
Principal Investigator: Susan M Meffert, MD, MPH University of California, San Francisco

Responsible Party: Susan Meffert, Associate Professor of Psychiatry, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT03466346     History of Changes
Other Study ID Numbers: 1U01MH115512 1R01MH113722-01A1
1U01MH115512 ( U.S. NIH Grant/Contract )
First Posted: March 15, 2018    Key Record Dates
Last Update Posted: January 16, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: NIMH Data Archive The National Institutes of Health (NIH) and NIMH have developed a federation of data repositories called the NIMH Data Archive (NDA) to store the collection of data from participants in research studies related to mental health, regardless of the source of funding. The extensive information collected by these studies, and subsequently stored in the National Database for Autism Research (NDAR), the NIH Pediatric MRI Repository (PedsMRI), the National Database for Clinical Trials Related to Mental Illness (NDCT), and the Research Domain Criteria Database (RDoCdb) provides a rare and valuable scientific resource. The NIH and the NIMH seek to encourage the use of these resources to achieve rapid scientific progress. In order to take full advantage of such resources and maximize their research value, it is important that data be made available, on appropriate terms and conditions, to the largest possible number of qualified investigators in a timely manner.
Supporting Materials: Study Protocol
Clinical Study Report (CSR)
Time Frame: Data will be made available to the NIMH data archive as soon as it is verified as clean and complete, with at least annual updates throughout the duration of the study. Data will be be available indefinitely or for as long as the NIMH repositories supports the electronic data storage.
Access Criteria: The investigative team and our NIMH and GACD partners will review requests for data. Evaluation will include scientific merit of the proposal, overlap versus building upon the study goals.

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Depression
Depressive Disorder
Stress Disorders, Post-Traumatic
Behavioral Symptoms
Mood Disorders
Mental Disorders
Stress Disorders, Traumatic
Trauma and Stressor Related Disorders
Fluoxetine
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Serotonin Agents
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Cytochrome P-450 CYP2D6 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors